Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases.
OBJECTIVE
The authors analyzed in a retrospective manner the prognostic significance of p53 and mdm-2 expression, DNA ploidy, S-phase fraction (SPF), and traditional clinical and pathological prognostic factors in patients with uterine leiomyosarcomas.


METHODS
Forty-nine patients were diagnosed with uterine leiomyosarcoma (25 stage I, 4 stage II, 8 stage III, and 12 stage IV). DNA flow cytometric analysis and immunohistochemical staining for p53 and mdm-2 were performed on paraffin-embedded archival tissue from the uterine tumors.


RESULTS
Of the 49 patients, 35 (71%) died of disease and 2 died of intercurrent disease. The 5-year survival rate was 33%. FIGO surgical stage, DNA ploidy, SPF, mitotic index, cellular atypia, and tumor grade obtained significance (P < 0.05) in a univariate survival analysis of the leiomyosarcomas. In a multivariate analysis with survival as the end point, stage was found to be the most important factor (P = 0.007); DNA ploidy (P = 0. 045) and SPF (P = 0.041) also had independent prognostic significance. For FIGO stage I tumors, DNA ploidy (P = 0.04) and tumor grade (P = 0.01) were statistically significant in a univariate analysis, while only grade had independent prognostic significance (P = 0.01) in a multivariate analysis. In a univariate analysis including only FIGO stage I and II tumors with disease-free survival as the end point, p53 overexpression (P = 0.0016), DNA ploidy (P = 0.042), and tumor grade (P = 0.008) obtained significance. In a multivariate analysis, only p53 had independent statistical significance (P = 0.01). All p53 immunopositive stage I-II tumors recurred within 28 months from diagnosis.


CONCLUSIONS
This study found that stage represents the most important prognostic factor for uterine leiomyosarcomas. DNA ploidy and SPF had independent prognostic value. DNA flow cytometry is useful in gaining additional prognostic information. In stage I patients, tumor grade gives significant information regarding clinical outcome. In addition, p53 overexpression may predict a higher risk of recurrence in early stage leiomyosarcomas.
Blom
R
R
Department of Gynecological Oncology, University Hospital, Linköping, Sweden.
Guerrieri
C
C
Stâl
O
O
Malmström
H
H
Simonsen
E
E
D002453:Cell Cycle; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007890:Leiomyosarcoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins; D011003:Ploidies; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology*
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2